Inner ear hair cells detect sound through deflection of mechanosensory stereocilia. Each stereocilium is supported by a paracrystalline array of parallel actin filaments that are packed more densely at the base, forming a rootlet extending into the cell body. The function of rootlets and the molecules responsible for their formation are unknown. We found that TRIOBP, a cytoskeleton-associated protein mutated in human hereditary deafness DFNB28, is localized to rootlets. In vitro, purified TRIOBP isoform 4 protein organizes actin filaments into uniquely dense bundles reminiscent of rootlets but distinct from bundles formed by espin, an actin crosslinker in stereocilia. We generated mutant Triobp mice (TriobpΔex8/Δex8) that are profoundly deaf. Stereocilia of TriobpΔex8/Δex8 mice develop normally but fail to form rootlets and are easier to deflect and damage. Thus, F-actin bundling by TRIOBP provides durability and rigidity for normal mechanosensitivity of stereocilia and may contribute to resilient cytoskeletal structures elsewhere.
|Number of pages||13|
|State||Published - May 2010|
Bibliographical noteFunding Information:
The authors thank M. Ikeya for advice and vectors, M. Streuli for mononclonal antiserum to TRIOBP-1/5, P. Belyantsev for drawings, and N. Gavara, M. Barzik, R. Chadwick, J. Schultz, and D. Drayna for discussions. This work was supported by NIDCD/NIH R01DC008861 and R01DC009434 to G.I.F., R01 DC004314 to J.R.B., the Wellcome Trust grant 071394/Z/03/Z to G.P.R., the HEC and MoST, Islamabad to S.R., intramural programs of NIDDK, NHLBI, and NIDCD Z01 DK060100 to J.E.H., Z01 DK060100 to J.A.H., Z01 HL004232-08 to J.S., Z01 DC 000064 to A.J.G., and Z01 DC000048 to T.B.F.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology (all)